Medicinal uses of indole MCQs With Answer

Indole is a privileged heterocyclic scaffold in medicinal chemistry, underlying many therapeutic agents and natural alkaloids relevant to B. Pharm students. This introduction focuses on medicinal uses of indole derivatives — from serotonin and melatonin (CNS modulators) to indomethacin (NSAID), sumatriptan (antimigraine), ergot and vinca alkaloids (vascular and anticancer agents). Key concepts covered include indole structure, biosynthesis from tryptophan, pharmacophore features, SAR, mechanisms of action, therapeutic applications, metabolism, and adverse effects. Mastering these topics helps students understand drug design, clinical uses, and safety of indole-based medicines. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which structural description best defines the indole core?

• Benzene ring fused to a pyrrole ring
• Pyridine ring fused to a pyrrole ring
• Two fused benzene rings
• Imidazole fused to benzene

Correct Answer: Benzene ring fused to a pyrrole ring

Q2. The indole nitrogen is characterized by which chemical property?

• Strongly basic due to free lone pair
• Weakly basic because the lone pair is part of aromaticity
• Strongly acidic with low pKa
• Highly nucleophilic at physiological pH

Correct Answer: Weakly basic because the lone pair is part of aromaticity

Q3. Which biosynthetic precursor gives rise to indole-containing natural products like serotonin?

• Phenylalanine
• Tryptophan
• Tyrosine
• Histidine

Correct Answer: Tryptophan

Q4. Serotonin is chemically known as:

• 3-indoleacetic acid
• 5-hydroxytryptamine
• N-acetyl-5-methoxytryptamine
• Indomethacin

Correct Answer: 5-hydroxytryptamine

Q5. Which enzyme catalyzes the rate-limiting step in serotonin biosynthesis from tryptophan?

• Tryptophan decarboxylase
• Tryptophan hydroxylase
• Aromatic L-amino acid decarboxylase
• Monoamine oxidase

Correct Answer: Tryptophan hydroxylase

Q6. Melatonin is derived from serotonin by which sequence of reactions?

• Methylation then acetylation
• Acetylation then methylation
• Hydroxylation then acetylation
• Decarboxylation then methylation

Correct Answer: Acetylation then methylation

Q7. Indomethacin, an indole derivative, primarily exerts its anti-inflammatory effect by:

• Blocking TNF-alpha receptors
• Inhibiting cyclooxygenase (COX) enzymes
• Antagonizing histamine H1 receptors
• Inhibiting phosphodiesterase

Correct Answer: Inhibiting cyclooxygenase (COX) enzymes

Q8. Which indole-based drug is a selective 5-HT1B/1D receptor agonist used for acute migraine?

• Indomethacin
• Sumatriptan
• Melatonin
• Reserpine

Correct Answer: Sumatriptan

Q9. Ergot alkaloids contain an indole moiety and are clinically associated with which primary pharmacological effect?

• Vasodilation mediated by nitric oxide
• Vasoconstriction via serotonergic and adrenergic receptors
• Peripheral beta-adrenergic blockade
• Calcium channel blockade

Correct Answer: Vasoconstriction via serotonergic and adrenergic receptors

Q10. Reserpine, an indole alkaloid, lowers blood pressure by which mechanism?

• Alpha-1 receptor blockade
• Inhibition of catecholamine synthesis
• Blocking vesicular monoamine transporter (VMAT) causing neurotransmitter depletion
• Calcium channel inhibition in vascular smooth muscle

Correct Answer: Blocking vesicular monoamine transporter (VMAT) causing neurotransmitter depletion

Q11. Indole-3-carbinol, found in cruciferous vegetables, is studied for which potential medicinal effect?

• Anticoagulant activity
• Anticancer and chemopreventive effects
• Strong opioid analgesia
• Hypoglycemic action

Correct Answer: Anticancer and chemopreventive effects

Q12. Which synthetic method is classical for constructing the indole ring in medicinal chemistry?

• Diels-Alder reaction
• Fischer indole synthesis
• Aldol condensation
• Claisen rearrangement

Correct Answer: Fischer indole synthesis

Q13. The 3-position of indole is often reactive in electrophilic substitution because:

• It bears a positive charge in the aromatic system
• The electron density is highest at C-3 due to resonance from nitrogen
• It is sterically hindered making it more reactive
• It has the highest pKa in the ring

Correct Answer: The electron density is highest at C-3 due to resonance from nitrogen

Q14. Which indole derivative acts as a sleep regulator and is used for insomnia and circadian rhythm disorders?

• Indomethacin
• Melatonin
• Indole-3-acetic acid
• Vincristine

Correct Answer: Melatonin

Q15. Vincristine and vinblastine contain indole subunits and primarily treat cancer by:

• DNA intercalation and strand breakage
• Inhibiting microtubule polymerization and mitotic spindle formation
• Inhibiting topoisomerase I
• Antimetabolite action on purine synthesis

Correct Answer: Inhibiting microtubule polymerization and mitotic spindle formation

Q16. Which metabolic enzyme family commonly metabolizes many indole-containing drugs?

• UDP-glucuronosyltransferases only
• CYP450 monooxygenases
• Proteases
• DNA polymerases

Correct Answer: CYP450 monooxygenases

Q17. Indole-3-acetic acid is best described as:

• A human neurotransmitter
• A plant auxin (growth hormone)
• An NSAID used clinically
• A synthetic opioid

Correct Answer: A plant auxin (growth hormone)

Q18. Which adverse effect is classically associated with chronic high-dose ergot alkaloid exposure?

• Hepatotoxicity without vascular effects
• Ergotism characterized by severe vasospasm and gangrene
• Selective renal tubular necrosis only
• Bronchospasm and allergic rash only

Correct Answer: Ergotism characterized by severe vasospasm and gangrene

Q19. The pharmacophore feature of indole important for binding many serotonin receptors is:

• Anionic carboxylate at position 2
• Planar bicyclic aromatic system with a hydrogen-bonding NH
• Large aliphatic side chain at position 6
• Quaternary ammonium at nitrogen

Correct Answer: Planar bicyclic aromatic system with a hydrogen-bonding NH

Q20. Which process degrades serotonin in neurons and peripheral tissues?

• COMT-mediated methylation
• Monoamine oxidase (MAO) oxidation
• Glutathionylation
• Peptidase cleavage

Correct Answer: Monoamine oxidase (MAO) oxidation

Q21. Indole derivatives that inhibit cyclooxygenase share which clinical risk profile?

• High risk of QT prolongation only
• Gastrointestinal ulceration and bleeding due to COX inhibition
• No adverse effects due to specificity
• Severe hyperkalemia routinely

Correct Answer: Gastrointestinal ulceration and bleeding due to COX inhibition

Q22. Which indole-containing drug is an anti-inflammatory derived from indole acetic acid and often used in rheumatology?

• Indomethacin
• Sumatriptan
• Melatonin
• Reserpine

Correct Answer: Indomethacin

Q23. In structure-activity relationship (SAR) of indole drugs targeting 5-HT receptors, substitution at which position of the indole ring often mimics the 5-hydroxy group of serotonin?

• Position 1 (nitrogen)
• Position 5 of the benzene ring
• Position 7 of the benzene ring only
• Position 2 on the pyrrole ring

Correct Answer: Position 5 of the benzene ring

Q24. Which clinical application best fits indole alkaloid vinca derivatives?

• Antimigraine acute therapy
• Anticancer chemotherapy for leukemias and lymphomas
• Antihypertensive first-line therapy in pregnancy
• Antiarrhythmic agent for atrial fibrillation

Correct Answer: Anticancer chemotherapy for leukemias and lymphomas

Q25. The indole nucleus contributes to blood-brain barrier penetration of CNS drugs primarily because it is:

• Highly polar and ionized at physiological pH
• Planar and relatively lipophilic facilitating passive diffusion
• Large and charged preventing CNS access
• Rapidly conjugated to glucuronides in blood

Correct Answer: Planar and relatively lipophilic facilitating passive diffusion

Q26. Which indole-based natural product was historically used for hypertension and psychotic disorders?

• Reserpine from Rauwolfia
• Indomethacin from synthetic sources
• Melatonin from pineal extracts only
• Sumatriptan from ergot

Correct Answer: Reserpine from Rauwolfia

Q27. Which of the following statements about indole fluorescence is correct and relevant in drug analysis?

• Indole ring systems are non-fluorescent and cannot be detected by fluorescence methods
• Many indole compounds are intrinsically fluorescent, aiding analytical detection
• Only protonated indoles fluoresce strongly
• Indole fluorescence is irrelevant in HPLC assays

Correct Answer: Many indole compounds are intrinsically fluorescent, aiding analytical detection

Q28. Which therapeutic class commonly includes indole scaffolds because of their 5-HT receptor activity?

• Anticoagulants
• Antimigraine (triptans) and antidepressants
• Loop diuretics
• Beta-lactam antibiotics

Correct Answer: Antimigraine (triptans) and antidepressants

Q29. Indole-containing indirubin has been investigated for which mechanism relevant to cancer therapy?

• Inhibition of cyclin-dependent kinases (CDKs)
• Activation of DNA polymerase
• Stimulating angiogenesis
• Blocking glucocorticoid receptors

Correct Answer: Inhibition of cyclin-dependent kinases (CDKs)

Q30. Which safety precaution is particularly important when prescribing ergot derivatives and triptans together?

• No interactions; they are safe to combine
• Risk of additive vasospasm and ischemia; avoid close coadministration
• They cause severe hypoglycemia when combined
• Combination leads to enhanced anticoagulation

Correct Answer: Risk of additive vasospasm and ischemia; avoid close coadministration

Q31. Which functional group modification on indole often increases water solubility of drug candidates?

• Introduction of bulky hydrophobic alkyl groups
• Addition of polar groups such as hydroxyl, carboxyl, or basic amines
• Removal of all heteroatoms
• Conversion to fully aromatic polycyclic system

Correct Answer: Addition of polar groups such as hydroxyl, carboxyl, or basic amines

Q32. Which indole-based agent is contraindicated in pregnancy due to teratogenic risk historically associated with ergot derivatives?

• Indomethacin only
• Ergotamine and dihydroergotamine
• Melatonin supplements
• Sumatriptan as routine prophylaxis

Correct Answer: Ergotamine and dihydroergotamine

Q33. The choice of indole scaffold in CNS drug design is often because:

• It cannot form hydrogen bonds with receptors
• It mimics endogenous indole neurotransmitters like serotonin
• It always prevents blood-brain barrier penetration
• It is inert and metabolically stable in all cases

Correct Answer: It mimics endogenous indole neurotransmitters like serotonin

Q34. Which laboratory reaction selectively protects the indole NH for further derivatization?

• Nitration without protection
• N-acetylation of the indole nitrogen
• Complete hydrogenation of the ring
• Oxidation to indole-2,3-dione

Correct Answer: N-acetylation of the indole nitrogen

Q35. For indole-based drugs, glucuronidation typically occurs at which sites to increase excretion?

• Nonpolar carbon atoms only
• Phenolic hydroxyl or secondary amine sites
• Indole carbon-3 exclusively
• Quaternary nitrogen centers only

Correct Answer: Phenolic hydroxyl or secondary amine sites

Q36. Which indole derivative is used as a probe for understanding serotonin receptor pharmacology in research?

• Indole-3-acetic acid
• 8-OH-DPAT (a 5-HT1A agonist)
• Acetaminophen
• Penicillin

Correct Answer: 8-OH-DPAT (a 5-HT1A agonist)

Q37. A common clinical adverse effect of indomethacin therapy is:

• Severe hyperkalemia
• Gastrointestinal bleeding and ulceration
• Profound lymphopenia as first-line toxicity
• Photosensitivity without GI effects

Correct Answer: Gastrointestinal bleeding and ulceration

Q38. Which statement about indole-containing natural products and drug discovery is correct?

• Natural indole alkaloids are a major source of scaffolds for anticancer and CNS drugs
• Natural indole compounds have no therapeutic relevance
• All natural indoles are too toxic for drug development
• Indole scaffolds are avoided in medicinal chemistry

Correct Answer: Natural indole alkaloids are a major source of scaffolds for anticancer and CNS drugs

Q39. Sumatriptan’s therapeutic effect in migraine is mainly due to:

• Systemic anti-inflammatory action
• Cranial vasoconstriction and inhibition of trigeminal neurotransmitter release via 5-HT1B/1D agonism
• Direct opioid receptor activation
• Blocking GABA receptors in the cortex

Correct Answer: Cranial vasoconstriction and inhibition of trigeminal neurotransmitter release via 5-HT1B/1D agonism

Q40. Which indole-related compound is a known plant hormone rather than a human drug?

• Melatonin
• Indole-3-acetic acid (IAA)
• Indomethacin
• Reserpine

Correct Answer: Indole-3-acetic acid (IAA)

Q41. Which analytical technique exploits indole fluorescence for quantitation in biological samples?

• UV-Vis absorbance only
• Fluorescence spectroscopy or HPLC with fluorescence detection
• Infrared spectroscopy only
• Atomic absorption spectroscopy

Correct Answer: Fluorescence spectroscopy or HPLC with fluorescence detection

Q42. Which statement is true regarding drug–drug interactions for indole-based psychotropic agents?

• They never interact with MAO inhibitors
• Combining serotonergic indole drugs with MAO inhibitors or SSRIs risks serotonin syndrome
• All indole drugs are safe with herbal supplements without interaction
• Indole psychotropics do not involve CYP metabolism

Correct Answer: Combining serotonergic indole drugs with MAO inhibitors or SSRIs risks serotonin syndrome

Q43. Indole compounds modified to create indolocarbazoles (e.g., staurosporine analogs) are mainly explored for:

• Antihypertensive diuretics
• Kinase inhibition and anticancer activity
• Anticoagulation therapy
• Antibiotic use against Gram-negative bacteria only

Correct Answer: Kinase inhibition and anticancer activity

Q44. Which property of indole derivatives can influence their oral bioavailability?

• Only color and odor matter
• Lipophilicity, pKa, metabolic stability, and permeability
• Presence of any aromatic ring guarantees 100% bioavailability
• Only molecular weight dictates bioavailability

Correct Answer: Lipophilicity, pKa, metabolic stability, and permeability

Q45. Which indole-based drug requires caution in patients with peptic ulcer disease due to its mechanism?

• Sumatriptan
• Indomethacin
• Melatonin
• Vincristine

Correct Answer: Indomethacin

Q46. Which natural source is known for producing indole alkaloids like reserpine?

• Digitalis species
• Rauwolfia species
• Penicillium fungi only
• Citrus fruits

Correct Answer: Rauwolfia species

Q47. In medicinal chemistry optimization, converting an indole to a bioisostere aims to:

• Increase toxicity while reducing efficacy
• Retain biological activity while improving ADME or safety
• Remove all aromaticity to increase binding
• Guarantee complete elimination of metabolism

Correct Answer: Retain biological activity while improving ADME or safety

Q48. Which clinical monitoring is important for a patient on long-term reserpine therapy?

• Regular liver enzyme panels only
• Monitoring for depression, orthostatic hypotension, and nasal congestion
• No monitoring is required for alkaloids
• Only blood glucose monitoring is necessary

Correct Answer: Monitoring for depression, orthostatic hypotension, and nasal congestion

Q49. Which modification of the indole ring often increases selectivity toward a specific receptor subtype in drug design?

• Random addition of halogens without rationale
• Strategic substitution at positions 2, 3, 5 or 6 guided by SAR and receptor modeling
• Complete removal of the NH group always
• Converting indole to a saturated cyclohexane always increases selectivity

Correct Answer: Strategic substitution at positions 2, 3, 5 or 6 guided by SAR and receptor modeling

Q50. Which practice improves safe use of indole-based medications in pharmacy practice?

• Ignoring patient history as indole drugs have no interactions
• Reviewing concomitant serotonergic drugs, pregnancy status, cardiovascular history, and monitoring adverse effects
• Prescribing ergot derivatives freely to pregnant patients
• Assuming all indole drugs are OTC and require no counseling

Correct Answer: Reviewing concomitant serotonergic drugs, pregnancy status, cardiovascular history, and monitoring adverse effects

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